Systems and methods for cannabis extraction

ABSTRACT

This disclosure provides methods and systems for the supercritical fluid extraction of cannabinoids from cannabis. The supercritical fluid extraction of cannabinoids is performed with carbon dioxide (CO2) balanced with one or more hydrocarbons, such as propane, propene, and propadiene. As demonstrated, the extraction can be carried out at maximum efficiency and energy savings while keeping the wax formation at minimum by lowering temperature. The methods and systems disclosed herein reduce the production time and safety/environmental hazards and are suitable for proper and safe extraction in non-GMP and GMP environments.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. § 119(e) to U.S.Provisional Patent Application No. 63/024,839, filed May 14, 2020. Theforegoing applications are incorporated by reference herein in itsentirety.

FIELD OF THE INVENTION

This invention relates to methods and systems for supercritical fluidextraction of cannabinoids and terpenes from cannabis and morespecifically relates to the supercritical fluid extraction ofcannabinoids and terpenes from cannabis using carbon dioxide balancedwith hydrocarbon(s).

BACKGROUND OF THE INVENTION

The chemical phenotypes of Cannabis are useful to classify the plantmaterial as drug- or fiber-type varieties, based on quantitativedifferences in the content of main cannabinoids present. The keydifference between these two is found in the potential content of theactive component 9-tetrahydrocannabinol (THC). A high content of THCclassifies as drug-type cannabis, while a low THC content (e.g., lessthan 0.2%) classifies as fiber-type cannabis or Hemp. Both THC andCannabidiol (CBD), a non-psychoactive cannabinoid, are neutral formcannabinoids, obtained after a non-enzymatic decarboxylation processoccurs to the acidic forms, 9-tetrahydrocannabinolic acid (THCA) andCannabidiol acid (CBDA) originally present in the plant material.

Food and cosmetic products developed from natural sources are gainingglobal popularity because of their proven better therapeutic effectsover synthetic ones. For this reason, extraction of plant-derivedbioactive compounds, including functional oil, has been extensivelyinvestigated. The cold press method is the most commonly used to extractthese oils, and it is deemed advantageous because of the low operatingtemperature suitable for keeping essential nutrients from possiblethermal degradation. However, this method entails some drawbacks,including low yield.

The extraction method features essentially define the quality of thefinal product. The extraction of cannabis to make other forms ofconcentrate is a function of the solubility of THC and othercannabinoids in different organic solvents (mainly hydrocarbons andalcohols). Solvents like methanol, ethanol, chloroform, butane, hexane,etc. are currently applied. However, safety considerations related totheir toxicity and flammability exist.

Accordingly, there exists a need for a method and system for cannabisextraction with improved yield and efficiency and reduced energyconsumption and safety/environmental hazards.

SUMMARY OF THE INVENTION

This disclosure addresses the need mentioned above in a number ofaspects. In one aspect, this disclosure provides a method for cannabisextraction. The method comprises (i) contacting cannabis plant materialwith a supercritical fluid solvent system comprising carbon dioxide(CO₂) and a hydrocarbon co-solvent; (ii) obtaining a first fraction ofthe supercritical fluid solvent system containing a first cannabisextract during a first period of time; (iii) obtaining a second fractionof the supercritical fluid solvent system containing a second cannabisextract during a second period of time; and (iv) removing the CO₂ andthe hydrocarbon co-solvent from the first fraction of the supercriticalfluid solvent system and the second fraction of the supercritical fluidsolvent system, thereby obtaining the first cannabis extract and thesecond cannabis extract.

In some embodiments, the first cannabis extract comprises terpene andthe second cannabis extract comprises cannabinoids. In some embodiments,the cannabis plant material comprises fresh frozen. In some embodiments,the first period of time is between about 2 minutes and about 30minutes. In some embodiments, the second period of time is between about30 minutes and about 24 hours.

In some embodiments, the hydrocarbon co-solvent is selected from thegroup consisting of propane, propene, propadiene, and a combinationthereof. In some embodiments, a molar ratio of CO₂ to the hydrocarbonco-solvent is between about 0.75 to about 0.25 and about 0.98 to about0.02. In some embodiments, a molar ratio of CO₂ to the hydrocarbonco-solvent is about 0.95 to about 0.05.

In some embodiments, the step of contacting cannabis plant material witha supercritical fluid solvent system is performed at a pressure betweenabout 500 psi and about 800 psi. In some embodiments, the step ofcontacting cannabis plant material with a supercritical fluid solventsystem is performed at a pressure between about 650 psi and about 800psi. In some embodiments, the step of contacting cannabis plant materialwith a supercritical fluid solvent system is performed at a temperaturebetween about 32° F. and about 38° F. In some embodiments, the step ofcontacting cannabis plant material with a supercritical fluid solventsystem is performed at a temperature between about 34° F. and about 36°F.

In some embodiments, the cannabis extract comprises terpene oil. In someembodiments, the extraction efficiency of terpene is at least 50% higherthan a predetermined reference value.

In some embodiments, the cannabis extract comprises one or morecannabinoids selected from the group consisting of: tetrahydrocannabinol(THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG),cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM),and a combination thereof.

In some embodiments, the cannabis plant material is processed fromCannabis sativa or Cannabis indica. In some embodiments, the methodfurther comprises grinding Cannabis sativa or Cannabis indica intoground cannabis plant material.

In some embodiments, the wax formation during the extraction process isreduced by at least 10% compared to a predetermined reference value. Insome embodiments, the wax formation during the extraction process isreduced by at least 50% compared to a predetermined reference value.

In some embodiments, the method further comprises purifying the cannabisextract by employing at least one of chromatography, adsorption,crystallization, distillation, liquid-liquid extraction, filtration,fractional distillation, precipitation, recrystallization, andsublimation.

In another aspect, this disclosure also provides a system for cannabisextraction. The system comprises (a) at least one extractor configuredto receive plant material and a supercritical fluid solvent systemcomprising CO₂ and a hydrocarbon co-solvent; (b) an accumulatorconnected to the extractor and configured to feed the supercriticalfluid solvent system to the extractor; and (c) at least one containerconnected to the extractor and configured to receive the extractgenerated from the plant material.

In some embodiments, the plant material is cannabis plant material. Insome embodiments, the plant material is processed from Cannabis sativaor Cannabis indica. In some embodiments, the plant material is coffee ortea leaves.

In some embodiments, the system further comprises a first reservoir forCO₂ and a second reservoir for the hydrocarbon co-solvent, wherein thefirst reservoir and the second reservoir are connected to theaccumulator and configured to feed CO₂ and the hydrocarbon co-solvent tothe accumulator in which CO₂ and the hydrocarbon co-solvent are blendedat a predetermined molar ratio.

In some embodiments, the system further comprises a heater connectedwith both the accumulator and the extractor, wherein the heater heatsthe supercritical fluid solvent system after the supercritical fluidsolvent system passes through the plant material in the extractor,whereby the heated supercritical fluid solvent system is fed back to theaccumulator.

In some embodiments, the hydrocarbon co-solvent is selected from thegroup consisting of propane, propene, propadiene, and a combinationthereof. In some embodiments, the predetermined molar ratio of carbondioxide to the hydrocarbon co-solvent is between about 0.75 to about0.25 and about 0.98 to about 0.02. In some embodiments, thepredetermined molar ratio of carbon dioxide to the hydrocarbonco-solvent is about 0.95 to about 0.05.

In some embodiments, the accumulator is configured to provide thesupercritical fluid solvent system with a pressure between about 650 psiand about 800 psi. In some embodiments, the accumulator is configured toprovide the supercritical fluid solvent system with a temperaturebetween about 32° F. and about 38° F.

In some embodiments, the extract comprises terpene oil. In someembodiments, the extract comprises one or more cannabinoids selectedfrom the group consisting of: tetrahydrocannabinol (THC), cannabidiol(CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC),cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV),cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin(CBGV), cannabigerol monomethyl ether (CBGM), and a combination thereof.

In some embodiments, the wax formation is reduced by at least 10%compared to a predetermined reference value.

The foregoing summary is not intended to define every aspect of thedisclosure, and additional aspects are described in other sections, suchas the following detailed description. The entire document is intendedto be related as a unified disclosure, and it should be understood thatall combinations of features described herein are contemplated, even ifthe combination of features are not found together in the same sentence,or paragraph, or section of this document. Other features and advantagesof the invention will become apparent from the following detaileddescription. It should be understood, however, that the detaileddescription and the specific examples, while indicating specificembodiments of the disclosure, are given by way of illustration only,because various changes and modifications within the spirit and scope ofthe disclosure will become apparent to those skilled in the art fromthis detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

A clear understanding of the key features of the invention summarizedabove may be had by reference to the appended drawings, which illustratethe method and system of the invention, although it will be understoodthat such drawings depict preferred embodiments of the invention and,therefore, are not to be considered as limiting its scope with regard toother embodiments which the invention is capable of contemplating.

FIG. 1 is an illustration of the method and system of this inventionshowing a simplified end-view diagram of an extractor that has beenutilized for this invention.

FIG. 2 is an illustration of extraction curves from CO₂ supercriticalextraction

FIG. 3 is an illustration of extraction curves from 0.95 CO₂/0.05propane, 0.95 CO2/0.05 propene, and 0.9 CO₂/0.05 allene (or propadiene)extractions versus CO₂ only method

FIG. 4 is an illustration of extraction curves from 0.9 CO₂/0.10propane, 0.90 CO₂/0.10 propene, and 0.90 CO₂/0.10 allene (or propadiene)extractions versus CO₂ only method

DETAILED DESCRIPTION OF THE INVENTION

This disclosure provides methods and systems for supercritical fluidextraction of cannabinoids from cannabis. The supercritical fluidextraction of cannabinoids is performed with CO₂ balanced with one ormore hydrocarbons, such as propane (C₃H₈), propene (C₃H₆), andpropadiene (C₃H₄), or a combination thereof. Importantly, the extractioncan be carried out at maximum efficiency and energy savings, whilekeeping the wax formation at a minimum by lowering temperature. Themethods and systems disclosed herein reduce the production time andsafety/environmental hazards and are suitable for proper and safeextraction in non-GMP and GMP environments.

A. Methods for Cannabis Extraction

In one aspect, this disclosure provides a method for cannabisextraction. The method comprises (i) contacting cannabis plant materialwith a supercritical fluid solvent system comprising CO₂ and ahydrocarbon co-solvent, to obtain a cannabis extract; and (ii) removingthe supercritical fluid system from the cannabis extract. In someembodiments, steps (a) and (b) may be repeated at least once.

The method comprises (i) contacting cannabis plant material with asupercritical fluid solvent system comprising carbon dioxide (CO₂) and ahydrocarbon co-solvent; (ii) obtaining a first fraction of thesupercritical fluid solvent system containing a first cannabis extractduring a first period of time; (iii) obtaining a second fraction of thesupercritical fluid solvent system containing a second cannabis extractduring a second period of time; and (iv) removing the CO₂ and thehydrocarbon co-solvent from the first fraction of the supercriticalfluid solvent system and the second fraction of the supercritical fluidsolvent system, thereby obtaining the first cannabis extract and thesecond cannabis extract.

In some embodiments, the first cannabis extract comprises terpene andthe second cannabis extract comprises cannabinoids. In some embodiments,the cannabis plant material comprises fresh frozen. In some embodiments,the first period of time is between about 2 minutes and about 30minutes. In some embodiments, the second period of time is between about30 minutes and about 24 hours.

“Fresh frozen,” as used herein, refers to plant materials taken beforethey are ready for drying and trimming into buds and frozen at about −5°C. to −10° C. Fresh frozen generally contains at least 50% to 70% waterby weight.

As used herein, “solvent system” refers to one or more solvents thatdissolve a solute (a chemically different liquid, solid or gas),resulting in a solution. The maximum quantity of solute that candissolve in a specific volume of solvent system varies with temperatureand pressure. The solvent system can have a specified polarity andproticity. As such, solvent system can be polar, nonpolar, protic, oraprotic, wherein each of these terms is used in a relative manner.

In some embodiments, the hydrocarbon co-solvent is selected from thegroup consisting of propane, propene, propadiene, and a combinationthereof. In some embodiments, a molar ratio of CO₂ to the hydrocarbonco-solvent is between about 0.75 to about 0.25 and about 0.98 to about0.02. In some embodiments, a molar ratio of CO₂ to the hydrocarbonco-solvent is about 0.95 to about 0.05.

In some embodiments, the step of contacting cannabis plant material witha supercritical fluid solvent system is performed at a pressure betweenabout 650 psi and about 800 psi. In some embodiments, the step ofcontacting cannabis plant material with a supercritical fluid solventsystem is performed at a temperature between about 32° F. and about 38°F.

Supercritical fluids offer a variety of applications due to theproperties that are easily adjusted with changing pressure andtemperature. Supercritical fluids extraction (SFE) has a worldwidecontribution to food, pharmaceutical, cosmetic, and oil industries as itoffers very high solvent recovery, simple separation, favorable thermalconditions, mass transfer properties, solvent-free products, andhealthier quality of products (M. Mukhopadhyay, et al., CRC Press, NewYork (2000); Fang, T., et al. Journal of Supercritical Fluids, vol. 40,no. 1: pp. 50-58 (2007)). Supercritical solvent extraction isadvantageous because the solvent can be removed completely from thesolutes of interest. It is an alternative method to replace or tocomplement conventional industrial processes, such as pressing andsolvent extraction. SFE is one of the promising technologies to separatevarious lipids, fatty acids, essential oil, etc. due to its effluentfree approach. The most frequently applied supercritical fluids includeargon, methane, ethane, carbon dioxide, propane, ammonia, and water.

As used herein, CO₂ is used as the main fluid for extraction of cannabisproducts due to its superior properties. It is economical, safe,non-flammable, non-toxic (no remaining residues in extract) and reachessupercritical conditions easily (32° C. and 7.38 MPa). Also, thelimitation of low polarity can be overwhelmed by the addition of a polarmodifier. Furthermore, optimization of SFE process parameters isessential to achieve maximum outputs with less investment. To date, veryfew studies related to optimization of SFE of hemp seed oil have beenreported. Carbon dioxide also has the advantage of low cost,availability, high purity, and its density is very sensitive to pressurechanges around the critical region. Supercritical CO₂ (scCO₂) candissolve low volatility substances, which enhances the concentration ofsolute in the supercritical phase far beyond the vapor pressure. Carbondioxide extraction improves the efficiency, selectivity, and yield ofvarious compounds from cannabis raw material.

SFE technique has many advantages over traditional methods, especiallyin preservation of thermosensitive compounds using low temperatures,which results in reduced energy consumption. The CBD and Δ9-THC thatform during decarboxylation are nonpolar and soluble in supercriticalCO₂. However, the waxes present in the flowers are also extracted bysupercritical CO₂. The removal of these waxes through the“winterization” process can generate a desirable increase in theconcentration of the cannabinoids in the extract. Syntactically, thisprocess consists of suspending the extract in n-hexane and thendecanting the waxes by severe cooling.

As disclosed herein, cannabis extracts with a high concentration ofΔ⁹-tetrahydrocannabinol acid (THCA) and Δ⁹-tetrahydrocannabinol (THC)can be obtained by supercritical CO₂ extraction. By finetuningextraction pressure and temperature, the CO₂ solvent strength can betuned, which provides selectivity to the extraction process. Regardlessof the rising popularity and usage of supercritical CO₂ extraction,there is very limited reported information about the efficiency of theextraction process for cannabis plant material, much less the favorableextraction conditions and cannabinoids concentration on the extracts.

The use of co-solvent, such as propane, propene, and/or propadiene inthe present disclosure, can improve the separation. However, the choiceof co-solvents depends on the system. Although these co-solvents cannotbe as flexibly manipulated through temperature and pressure as CO₂, theyproduce very similar results, sometimes better. For example, propane hasa small loading ratio of 1-4 volumes, and it can be recovered quickly.This means much faster production times. Also, it is an all-natural,organic solvent and leaves no toxic residues. Importantly, because itworks at relatively low pressures, e.g., 80-150 psi, the methods asdisclosed herein cost much less than a full supercritical CO₂ system andare superior in terms of quality and speed of production. Accordingly,the present invention offers advantages over conventional extractionmethods, including increased selectivity, automaticity, environmentalsafety, superior quality of extracts, and drastically decreased solventresidue.

As used herein, “extract” refers to a substance obtained by extracting araw material, using, for example, the disclosed supercritical solventsystem. The term “cannabis extract” refers to a substance obtained byextracting Cannabis (or any part thereof). For example, the process ofextracting a raw cannabis material using a solvent includes a hotsolvent extraction. In another example, the process of extracting a rawmaterial using a solvent includes supercritical fluid extraction (SFE),e.g., a fractional supercritical fluid extraction (FSFE).

In some embodiments, the cannabis extract comprises terpene oil. In someembodiments, the extraction efficiency of terpene is at least 50% higherthan a predetermined reference value. As used herein, “terpene” refersto a hydrocarbon or derivative thereof, found as a natural product andbiosynthesized by oligomerization of isoprene units. A terpene can beacyclic, monocyclic, bicyclic, or multicyclic. Examples includelimonene, pulegone, caryophyllene epoxide, and the like.

Terpenes are organic hydrocarbons that occur naturally in the essentialoils of plants. Technically, terpenes are a combination of carbon andhydrogen. Though the names are used interchangeably, terpenoids areterpenes that have been altered through a drying process. Terpenes areresponsible for the smell of cannabis, not only have their ownindividual medicinal properties, but they also work in conjunction witheach other and the other cannabinoids to create the overall effect of astrain.

Terpenes are responsible for the scent and flavor of individual cannabisstrains. The to concentration of terpenes can provide as many benefitsas potency and cannabinoid content. From anti-inflammatory to chronicpain relief, the world of cannabis terpenes offers an impressive varietyof therapeutic properties. These compounds define the flavor and aromaof our favorite plant but can also alter the high from cannabis.

Terpenes can intensify or downplay the effects of the cannabinoids.Carbonization destroys many of the terpenes, just like it destroys manyof the cannabinoids. Like cannabinoids, terpenes have their ownindividual optimal temperature, and these temperatures can vary widely.As the demand for terpene-rich products has increased, a variety ofproduct lines have come out, featuring cannabis concentrates infusedwith isolated terpenes.

In some embodiments, the cannabis extract comprises one or morecannabinoids selected from the group consisting of: tetrahydrocannabinol(THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG),cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM),and a combination thereof.

In some embodiments, the cannabis plant material is processed fromCannabis sativa or Cannabis indica. The cannabis plant material may ormay not need to be pre-processed. For example, the raw cannabis plantmaterial can be used directly for cannabis extraction. In someembodiments, the method further comprises grinding Cannabis sativa orCannabis indica into ground cannabis plant material.

As used herein, “Cannabis sativa L.” or “Cannabis sativa” refers to anannual herbaceous plant in the Cannabis genus, a species of theCannabaceae family. As used herein, “Cannabis indica Lam” or “Cannabisindica” refers to an annual plant in the Cannabaceae family. A putativespecies of the genus Cannabis, it is typically distinguished fromCannabis sativa. Cannabis sativa and Cannabis indica can interbreed, sothe two strains can be viewed as sub-species or landraces. Interbredstains comprising genetic material from both sativa and indica strainscan be termed “sativa-dominant” or “indica-dominant,” depending uponperceived physical and psychotropic properties of the hybrids. The mixedinterbred strains can be themselves reproductively viable.

As used herein, “Cannabis ruderalis Janisch” or “Cannabis ruderalis”refers to a species of Cannabis originating in central Russia. Itflowers earlier than C. indica or C. sativa, does not grow as tall, andcan withstand much harsher climates than either of them. Cannabisruderalis will produce flowers based on its age, rather than light cycle(photoperiod) changes which govern flowering in C. sativa and C. indicavarieties. This kind of flowering is also known as “auto flowering.”

As used herein, “Cannabis” refers to a genus of flowering plants thatincludes a single species, Cannabis sativa, which is sometimes dividedinto two additional species, Cannabis indica and Cannabis ruderalis.These three taxa are indigenous to Central Asia, and South Asia.Cannabis has long been used for fiber (hemp), for seed and seed oils,for medicinal purposes, and as a recreational drug. Various extractsincluding hashish and hash oil are also produced from the plant.Suitable strains of Cannabis include, e.g., Indica-dominant (e.g.,Blueberry, BC Bud, Holland's Hope, Kush, Northern Lights, Purple, andWhite Widow), Pure sativa (e.g., Acapulco Gold and Malawi Gold(Chamba)), and Sativa-dominant (e.g., Charlotte's Web, Diesel, Haze,Jack Herer, Shaman, Skunk, Sour, and Te Puke Thunder). Cannabis plantmaterial can include any physical part of the plant material, including,e.g., the leaf, bud, flower, trichome, seed, or combination thereof.Likewise, the cannabis plant material can include any substancephysically derived from cannabis plant material, e.g., kief and hashish.

As used herein, “kief” refers to the resin glands (or trichomes) ofCannabis, which may accumulate in containers or be sifted from loose drycannabis flower with a mesh screen or sieve. Kief typically contains amuch higher concentration of psychoactive cannabinoids, such as THC,than that of the cannabis flowers from which it is derived.Traditionally, kief has been pressed into cakes of hashish forconvenience in storage, but can be vaporized or smoked in either form.

As used herein, “hashish” refers to a cannabis product composed ofcompressed or purified preparations of stalked resin glands, calledtrichomes. It contains the same active ingredients—such as THC and othercannabinoids—but in higher concentrations than unsifted buds or leaves.

As used herein, “leaf” refers to an organ of a vascular plant, asdefined in botanical terms, and in particular, in plant morphology. Inreference to cannabis, the first pair of leaves usually have a singleleaflet, the number gradually increasing up to a maximum of aboutthirteen leaflets per leaf (usually seven or nine), depending on varietyand growing conditions. At the top of a flowering plant, this numberagain diminishes to a single leaflet per leaf. The lower leaf pairsusually occur in an opposite leaf arrangement and the upper leaf pairsin an alternate arrangement on the main stem of a mature plant.

As used herein, “bud” refers to a flower-bearing stem or branch of thecannabis plant, especially a stem or branch bearing a mass of femaleflowers with associated leaves. The stem or branch bearing the femaleflowers can be fresh or can be dried. The pistils of the female cannabisflower are surrounded by a mass of trichome-rich petals and leaves andcan contain higher concentrations of cannabinoids than do the plantleaves or stems. A bud, e.g., a mass of female flowers and associatedleaves, usually covered with trichomes, can be further processedmechanically, i.e., “trimming” or “cleaning” the stem bearing the femaleflowers by removal of larger leaves and stem material. Buds, and cleanedbuds, can be used as a cannabis plant material in practice of a methodof the invention.

As used herein, “trichome” refers to a fine outgrowth or appendage onplants and certain protists. They are of diverse structure and function.Examples are hairs, glandular hairs, scales, and papillae. In referenceto cannabis, the trichome is a glandular trichome that occurs mostabundantly on the floral calyxes and bracts of female plants.

As used herein, “seed” refers to an embryonic plant enclosed in aprotective outer covering called the seed coat, usually with some storedfood. It is a characteristic of spermatophytes (gymnosperm andangiosperm plants) and the product of the ripened ovule, which occursafter fertilization and some growth within the mother plant. Theformation of the seed completes the process of reproduction in seedplants (started with the development of flowers and pollination), withthe embryo developed from the zygote and the seed coat from theinteguments of the ovule.

One of the advantages of the disclosed methods is that they result insignificantly reduced wax formation during the extraction process. Thus,the degumming and dewaxing process in the conventional extractionmethods can be eliminated. As a result, the present invention reducesenergy consumption and production cost/time. In some embodiments, thewax formation during the extraction process is reduced by at least 10%compared to a predetermined reference value.

In some embodiments, the method further comprises purifying the cannabisextract by employing at least one of chromatography, adsorption,crystallization, distillation, liquid-liquid extraction, filtration,fractional distillation, precipitation, recrystallization, andsublimation.

As used herein, “purifying” refers to a process of rendering asubstance, or a set of substances, pure, i.e., substantially free of, orhaving a lower relative content of, undesirable components. For example,the purified substance can be at least about 90% pure, at least about95% pure, or at least about 98% pure.

B. Systems for Cannabis Extraction

In another aspect, this disclosure also provides a CO₂/hydrocarbonextraction system, as represented schematically in FIG. 1 .

As depicted in TABLE 1. depending on trim potency, which varies from 8%to 12%, the cannabinoids potency results and efficiency will increase.The range and detailed experimental results can be observed as follows:

TABLE 1 Experiment Results for Trim Potency from 8% to 12% for CO₂ OnlyExtraction CO₂ Extraction Trim Potency (%) Cannabinoids Potency Results(%) Efficiency (%) 8 53 54 8 54 56 8 56 58 8 52 52 8 54 56 8 57 59 8 5557 8 53 55 9 53 57 9 55 58 9 54 58 9 56 59 9 55 58 9 57 59 9 54 58 9 5759 10 55 59 10 56 61 10 58 62 10 55 59 10 56 59 10 56 59 10 58 62 10 5761 11 56 60 11 61 63 11 60 62 11 58 61 11 59 61 11 57 60 11 61 63 11 6062 12 64 66 12 63 65 12 61 63 12 62 64 12 63 65 12 63 65 12 64 66 12 6264

In some embodiments, the extraction system may include at least oneextractor and at least one heating system (heater). In some embodiments,the extraction system may include, for example, 1 to 30 extractors inparallel. Each extractor may have various capacities, e.g., 20 L, assupported by two CO₂/hydrocarbon pumping systems (one for gas and onefor liquid).

The heating system heats up the extracted oil up to 115° F. and thedepressurized liquid mixture from the top of the extractor to about180-480 psi (depending on the hydrocarbon and its fraction in blend) andgasifies the blend. In some embodiments, the extraction system mayinclude at least one condensing system to cool down and liquefy the gasblend at 650-800 psi so as to keep the trim vessel cold to ensure thatno waxes are being produced in the final product and two extractcollection vessels, such as cannabinoid oil vessel and terpene vessel.All equipment are sized and configured to satisfy the output of theextractor(s).

The trim is fed to the extractor vessel initially. The next step is tofeed CO₂ and hydrocarbon from the respective reservoirs (e.g., CO2reservoir, hydrocarbon reservoir) to the accumulator in proper molefractions. Both the accumulator and extractor vessels are kept at lowtemperatures (32-38° F.) to ensure there will be no waxes in the finalproduct. The accumulator pressure is above 650-800 psi, with theCO₂/hydrocarbon existing as liquid therein.

The gas mixture is recycled with a loop, as shown in FIG. 1 . The liquidblend will then be depressurized to proper pressure, e.g., by valve 3 inFIG. 1 , and the heater will provide proper temperature to get into thegas phase. The gas blend then cooled down and fed to the extractor in aloop.

The trim vessel pressure is kept at 1050-1200 psi and 32-38° F. to keepthe extraction efficiency high. Another novel feature of this extractionsystem is the capability of controlling the temperature inside theextractor. The gas blend stays in the gas phase under specific pressureand temperature. By expanding the blend at lower pressure, thetemperature inside the extractor will drop, which helps to control theamount of waxes in the final product without requiring any externalcooling system. The cold temperature inside the extractor ensures nowaxes are being separated and produced in the final product vessel.

Adding hydrocarbons, such as propane and propene, as co-solvents to CO₂will strongly increase potency results from 52-64% to 75-92%. Theextraction efficiency will also increase from 56-66% to 79-95%. Terpenesextraction yield is also increased by up to 90%. Adding 5-10% ofpropane/propene/propadiene will significantly decrease energyconsumption for the compressor up to 45%. It should be mentioned thatpropene and propadiene act stronger compared to propane, and the potencyresults for propadiene is slightly higher than propane and propene

The detailed experimental results for different trim potency andCO₂/Hydrocarbon extraction are given in Table 2.

TABLE 2 Experiment Results for Trim Potency from 8% to 12% forCO₂/Hydrocarbon Extraction CO₂/Hydrocarbon Trim Potency (%) CannabinoidsPotency Results (%) Efficiency (%) 8 76 77 8 77 78 8 75 76 8 79 80 8 8384 8 81 82 8 80 81 8 82 83 9 78 82 9 84 87 9 85 88 9 86 89 9 83 86 9 8386 9 82 85 9 85 88 10 82 87 10 79 85 10 86 90 10 88 92 10 88 92 10 86 9010 87 91 10 85 89 11 84 87 11 90 93 11 89 92 11 88 91 11 89 92 11 90 9311 87 90 11 86 89 12 88 88 12 92 95 12 91 91 12 90 90 12 92 95 12 90 9012 87 87 12 86 86

The current temperature for the trim vessel is 95-115° F., which willresult in wax formation in the final oil. Reducing the temperature inthe trim vessel to 32° F. (or even lower) will minimize the waxformation in the final product. Therefore, there is no need for adewaxing/degumming process, which will result in more expenses savings.

In another aspect, this disclosure also provides a system for cannabisextraction. The system comprises (a) at least one extractor configuredto receive plant material and a supercritical fluid solvent systemcomprising CO₂ and a hydrocarbon co-solvent; (b) an accumulatorconnected to the extractor and configured to feed the supercriticalfluid solvent system to the extractor; and (c) at least one containerconnected to the extractor and configured to receive the extractgenerated from the plant material.

In some embodiments, the plant material is cannabis plant material. Insome embodiments, the plant material is processed from Cannabis sativaor Cannabis indica.

In some embodiments, the system further comprises a first reservoir forCO₂ and a second reservoir for the hydrocarbon co-solvent, wherein thefirst reservoir and the second reservoir are connected to theaccumulator and configured to feed CO₂ and the hydrocarbon co-solvent tothe accumulator in which CO₂ and the hydrocarbon co-solvent are blendedat a predetermined molar ratio.

In some embodiments, the system further comprises a heater connectedwith both the accumulator and the extractor, wherein the heater heatsthe supercritical fluid solvent system after the supercritical fluidsolvent system passes through the plant material in the extractor,whereby the heated supercritical fluid solvent system is fed back to theaccumulator.

In some embodiments, the hydrocarbon co-solvent is selected from thegroup consisting of propane, propene, propadiene, and a combinationthereof. In some embodiments, the predetermined molar ratio of carbondioxide to the hydrocarbon co-solvent is between about 0.75 to about0.25 and about 0.99 to about 0.01 (e.g., 0.8:0.2; 0.85:0.15; 0.9:0.1;0.92:0.08; 0.94:0.06; 0.95:0.05; 0.96:0.04; 0.98:0.02). In someembodiments, the predetermined molar ratio of carbon dioxide to thehydrocarbon co-solvent is about 0.95 to about 0.05.

In some embodiments, the accumulator is configured to provide thesupercritical fluid solvent system with a pressure between about 650 psiand about 800 psi. In some embodiments, the accumulator is configured toprovide the supercritical fluid solvent system with a temperaturebetween about 32° F. and about 38° F.

In some embodiments, the extract comprises terpene oil. In someembodiments, the extract comprises one or more cannabinoids selectedfrom the group consisting of: tetrahydrocannabinol (THC), cannabidiol(CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC),cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV),cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin(CBGV), cannabigerol monomethyl ether (CBGM), and a combination thereof.

In some embodiments, the wax formation is reduced by at least 10%compared to a predetermined reference value.

The disclosed systems and methods are also amenable for producinginfused coffee/tea. In some embodiments, the plant material is coffee ortea leaves. The coffee/tea leaves can be fed to the extractor(s) withtrim at the same operating conditions (temperature and pressures), asmentioned above. The cold temperature ensures high-quality coffee/teaproduction.

C. Compositions for Cannabis Extracts

In another aspect of this disclosure, also provided is a compositioncomprising the cannabis extract prepared by the method and system asdescribed above. The composition further comprises an additive, apharmaceutical acceptable carrier, or an adjuvant to the cannabiscomponent.

The composition can be an oral dosage composition, a pulmonary or nasaldosage composition, or a topical dosage composition. The compositionscan be in the form of a solution, a spray, or a powder. In someembodiments, the composition is in the form of a tablet, a capsule, ajelly, a cream, an ointment, a suspension, a spray, or a chewing gum.

In certain embodiments, the compositions as described herein areadministered via a vaporizer or like device as described, for example,in U.S. Pat. No. 8,915,254; U.S. Pat. Appl. Pub. No. 2014/0060552; U.S.Pat. No. 8,488,952; and U.S. Pat. Appl. Pub. No. 2015/0040926.Compositions for pulmonary administration also include, but are notlimited to, dry powder compositions consisting of the powder of acannabis oil described herein, and the powder of a suitable carrierand/or lubricant. The compositions for pulmonary administration can beinhaled from any suitable dry powder inhaler device known to a personskilled in the art. In certain instances, the compositions may beconveniently delivered in the form of an aerosol spray from pressurizedpacks or a nebulizer, with the use of a suitable propellant, forexample, dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane, carbon dioxide, or other suitable gas. In thecase of a pressurized aerosol, the dosage unit can be determined byproviding a valve to deliver a metered amount. Capsules and cartridgesof, for example, gelatin for use in an inhaler or insufflator can beformulated containing a powder mix of the compound(s) and a suitablepowder base, for example, lactose or starch.

Pharmaceutical compositions or medicaments can be formulated by standardtechniques or methods well-known in the art of pharmacy using one ormore physiologically acceptable carriers or excipients. Suitablepharmaceutical carriers are described herein and in, e.g., “Remington'sPharmaceutical Sciences” by E. W. Martin. Cannabis oil extracts can beformulated for administration by any suitable route, including, but notlimited to, orally, topically, nasally, rectally, vaginally, pulmonary,parenterally (e.g., intravenously, subcutaneously, intramuscularly,etc.), and combinations thereof. In some embodiments, the cannabis oilis diluted in a liquid, e.g., a carrier oil. The most suitable route ofadministration in any given case will depend in part on the conditionbeing treated as well as the response of the subject to the particularroute of treatment.

For oral administration, a pharmaceutical composition or a medicamentcan take the form of, e.g., a tablet or a capsule prepared byconventional means with a pharmaceutically acceptable excipient.Preferred are tablets and gelatin capsules comprising the activeingredient(s), together with (a) diluents or fillers, e.g., lactose,dextrose, sucrose, mannitol, maltodextrin, lecithin, agarose, xanthangum, guar gum, sorbitol, cellulose (e.g., ethyl cellulose,microcrystalline cellulose), glycine, pectin, polyacrylates and/orcalcium hydrogen phosphate, calcium sulfate, (b) lubricants; e.g.,silica, anhydrous colloidal silica, talcum, stearic acid, its magnesiumor calcium salt (e.g., magnesium stearate or calcium stearate), metallicstearates, colloidal silicon dioxide, hydrogenated vegetable oil, cornstarch, sodium benzoate, sodium acetate and/or polyethyleneglycol; fortablets also (c) binders, e.g., magnesium aluminum silicate, starchpaste, gelatin, tragacanth, methylcellulose, sodiumcarboxymethylcellulose, polyvinylpyrrolidone and/or hydroxypropylmethylcellulose; if desired (d) disintegrants, e.g., starches (e.g.,potato starch or sodium starch), glycolate, agar, alginic acid or itssodium or potassium salt, or effervescent mixtures; (e) wetting agents,e.g., sodium lauryl sulfate, and/or (f) absorbents, colorants, flavors,and sweeteners. Tablets can be either uncoated or coated according tomethods known in the art. The excipients described herein can also beused for preparation of buccal dosage forms and sublingual dosage forms(e.g., films and lozenges) as described, for example, in U.S. Pat. Nos.5,981,552 and 8,475,832. Formulation in chewing gums as described, forexample, in U.S. Pat. No. 8,722,022, is also contemplated.

Further preparations for oral administration can take the form of, forexample, solutions, syrups, suspensions, and toothpastes. Liquidpreparations for oral administration can be prepared by conventionalmeans with pharmaceutically acceptable additives, for example,suspending agents, for example, sorbitol syrup, cellulose derivatives,or hydrogenated edible fats; emulsifying agents, for example, lecithin,xanthan gum, or acacia; non-aqueous vehicles, for example, almond oil,sesame oil, hemp seed oil, fish oil, oily esters, ethyl alcohol, orfractionated vegetable oils; and preservatives, for example, methyl orpropyl-p-hydroxybenzoate or sorbic acid. The preparations can alsocontain buffer salts, flavoring, coloring, and/or sweetening agents asappropriate.

Typical formulations for topical administration include creams,ointments, sprays, lotions, hydrocolloid dressings, and patches, as wellas eye drops, ear drops, and deodorants. Cannabis oils can beadministered via transdermal patches as described, for example, in U.S.Pat. Appl. Pub. No. 2015/0126595 and U.S. Pat. No. 8,449,908.Formulation for rectal or vaginal administration is also contemplated.The cannabis oils can be formulated, for example, using suppositoriescontaining conventional suppository bases such as cocoa butter and otherglycerides as described in U.S. Pat. Nos. 5,508,037 and 4,933,363.Compositions can contain other solidifying agents such as shea butter,beeswax, kokum butter, mango butter, illipe butter, tamanu butter,carnauba wax, emulsifying wax, soy wax, castor wax, rice bran wax, andcandelilla wax. Compositions can further include clays (e.g., Bentonite,French green clays, Fuller's earth, Rhassoul clay, white kaolin clay)and salts (e.g., sea salt, Himalayan pink salt, and magnesium salts suchas Epsom salt).

The compositions set forth herein can be formulated for parenteraladministration by injection, for example, by bolus injection orcontinuous infusion. Formulations for injection can to be presented inunit dosage form, for example, in ampoules or in multi-dose containers,optionally with an added preservative. Injectable compositions arepreferably aqueous isotonic solutions or suspensions, and suppositoriesare preferably prepared from fatty emulsions or suspensions. Thecompositions may be sterilized and/or contain adjuvants, such aspreserving, stabilizing, wetting or emulsifying agents, solutionpromoters, salts for regulating the osmotic pressure, buffers, and/orother ingredients. Alternatively, the compositions can be in powder formfor reconstitution with a suitable vehicle, for example, a carrier oil,before use. In addition, the compositions may also contain othertherapeutic agents or substances.

The compositions can be prepared according to conventional mixing,granulating, and/or coating methods and contain from about 0.1 to about75%, preferably from about 1 to about 50%, of the cannabis oil extract.In general, subjects receiving a cannabis oil composition orally areadministered doses ranging from about 1 to about 2000 mg of cannabisoil. A small dose ranging from about 1 to about 20 mg can typically beadministered orally when treatment is initiated, and the dose can beincreased (e.g., doubled) over a period of days or weeks until themaximum dose is reached.

In some embodiments, the composition is an oral dosage composition, apulmonary or nasal dosage composition, or a topical dosage composition.The composition may be in the form of a solution, a spray, or a powder,a tablet, a capsule, a jelly, a cream, an ointment, a suspension, aspray, or a chewing gum.

Also within the scope of this disclosure is a unit dose of thecomposition as described above. In some embodiments, the unit dosecomprises an amount of the composition selected from the groupconsisting of: trace amount, 0.01-0.05 mg, 0.05-0.1 mg, 0.1-0.5 mg,0.25-1 mg, 0.5-15 mg, 0.5-2.5 mg, 1.0-2.5 mg, 2.5-5 mg, 5.0-7.5 mg,5.0-10 mg, 1.0-25 mg, 25-50 mg, 50-75 mg, 75-100 mg, 10-20 mg, 10-15 mg,and 15-20 mg, 20-30 mg, 30-40 mg, 40-50 mg, 50-60 mg, 60-70 mg, 70-80mg, 80-90 mg, 90-100 mg, 1-100 mg, 100-125 mg, 125-150 mg, 150-175 mg,175-200 mg, and >200 mg.

In some embodiments, the composition may further comprise a second agentselected from the group consisting of: cannabinoids, terpenes,anti-insomnia, anti-tussive, opioid analgesic, decongestant, non-opioidanalgesic/anti-inflammatory drug, anti-migraine drug, anti-emetic,anti-histamine, proton pump inhibitor, H2 antagonist/H2 blocker,tranquilizer, anticonvulsant, hypnotic, muscle relaxant, anti-psychotic,anti-diarrheal, Attention Deficit and Hyperactivity Disorder (ADHD)drug, anti-Parkinson disease drug, benzodiazepine, benzodiazepineantagonist, barbiturate, barbiturate antagonist, stimulant, stimulantantagonist, antidepressant, nutraceutical, nicotine, BCS Class II activeingredient, BCS Class IV active ingredient, an anti-multiple sclerosis(MS) drug, ethyl pyruvate, melatonin, caffeine, resveratrol, and acombination thereof.

In some embodiments, the second agent is selected from the groupconsisting of: CBD, THC, CBN, CBG, CBC, THCA, CBDA, THCV, and acombination thereof.

In some embodiments, the composition at therapeutically effectiveconcentrations or dosages be combined with a pharmaceutically orpharmacologically acceptable carrier, excipient or diluent, eitherbiodegradable or non-biodegradable.

For example, the composition may be administered in the pure form or ina pharmaceutically acceptable formulation including suitable elixirs,binders, and the like (also generally referred to a “carriers”) or aspharmaceutically acceptable salts (e.g., alkali metal salts such assodium, potassium, calcium or lithium salts, ammonium, etc.) or othercomplexes. It should be understood that the pharmaceutically acceptableformulations include liquid and solid materials conventionally utilizedto prepare both injectable dosage forms and solid dosage forms such astablets and capsules and aerosolized dosage forms. In addition, thecompounds may be formulated with aqueous or oil-based vehicles. Watermay be used as the carrier for the preparation of compositions (e.g.,injectable compositions), which may also include conventional buffersand agents to render the composition isotonic. Other potential additivesand other materials (preferably those which are generally regarded assafe [GRAS]) include: colorants; flavorings; surfactants (TWEEN, oleicacid, etc.); solvents, stabilizers, elixirs, and binders or encapsulants(lactose, liposomes, etc). Solid diluents and excipients includelactose, starch, conventional disintegrating agents, coatings and thelike. Preservatives such as methylparaben or benzalkonium chloride mayalso be used. Depending on the formulation, it is expected that theactive composition will consist of about 1% to about 99% of thecomposition and the vehicular “carrier” will constitute about 1% toabout 99% of the composition. The pharmaceutical compositions of thepresent invention may include any suitable pharmaceutically acceptableadditives or adjuncts to the extent that they do not hinder or interferewith the therapeutic effect of the active compound.

Examples of carriers include, but are by no means limited to, forexample, poly(ethylene-vinyl acetate), copolymers of lactic acid andglycolic acid, poly(lactic acid), gelatin, collagen matrices,polysaccharides, poly(D,L lactide), poly(malic acid),poly(caprolactone), celluloses, albumin, starch, casein, dextran,polyesters, ethanol, methacrylate, polyurethane, polyethylene, vinylpolymers, glycols, mixtures thereof and the like. Standard excipientsinclude gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth,stearic acid, benzalkonium chloride, calcium stearate, glycerylmonostearate, cetostearyl alcohol, cetomacrogol emulsifying wax,sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene castoroil derivatives, polyoxyethylene sorbitan fatty acid esters,polyethylene glycols, polyoxyethylene stearates, colloidal silicondioxide, phosphates, sodium dodecyl sulfate, carboxymethylcellulosecalcium, carboxymethylcellulose sodium, methylcellulose,hydroxyethylcellulose, hydroxypropyl cellulose,hydroxypropyl-methylcellulose phthalate, noncrystalline cellulose,magnesium aluminum silicate, triethanolamine, polyvinyl alcohol,polyvinylpyrrolidone, sugars, and starches. See, for example, Remington:The Science and Practice of Pharmacy, 1995, Gennaro ed.

In some embodiments, the chemicals can be purified and blended togetherto produce a formulation similar in form to that for Marinol®. In theseformulations, the active ingredient is dissolved in sesame seed oil orsimilar oil and enclosed in a gel-capsule. In other embodiments, theformulation may be arranged to be used as an injectable or as anaerosol. In these embodiments, as will be apparent to one of skill inthe art, the appropriate pharmaceutically-acceptable additives may beadded so that the pharmaceutical composition is in the appropriate form.

As will be appreciated by one knowledgeable in the art, the formulationmay be used as, for example, an anti-emetic, appetite stimulant, or as atreatment for nausea, dementia, Alzheimer's disease, glaucoma, highblood pressure, inflammation or multiple sclerosis. For example, whenadministered to an individual in need of such treatment, thepharmaceutical composition of Δ⁸-THC and CBD will accomplish at leastone of the following: reduce nausea, promote or stimulate appetite,reduce vomiting and/or promote a general feeling of well-being.

Additional Ingredients

Cannabinoids are susceptible to oxidation and hydrolysis. Over time itis possible for cannabinoids to be exposed to oxygen, hydrogen ions(acids, water), in addition to any other environmental factors that willcause their degradation.

Organic bases can be used to prevent the degradation of thecannabinoids. These organic bases include, but are not limited to, butylhydroxyl anisole (BHA), butyl hydroxyl toluene (BHT), and sodiumascorbate; at concentrations between 0.001 to 5%>w/w, for example.Organic bases such as the following can improve the stability ofcannabinoids from chemical degradation for up to 2 years: BHA 0.001 to5% w/w, BHT 0.001 to 5% w/w, and combinations of BHA and BHT can also beused.

Antioxidants can be used to prevent or at least inhibit or mitigate thedegradation of cannabinoids from oxidation. Examples of antioxidantsinclude: ethanol, polyethylene glycol 300, polyethylene glycol 400,propylene glycol, propylene carbonate, N-methyl-2-pyrrolidones,dimethylacetamide, dimethyl sulfoxide, hydroxypropyl-P-cyclodextrins,sulfobutylether-β-cyclodextrin, a-cyclodextrin, HSPC phospholipid, DSPGphospholipid, DMPC phospholipid, DMPG phospholipid, ascorbyl palmitate,butylated hydroxyanisole, butylated hydroxyanisole, propyl gallate,a-tocopherol, γ-tocopherol, propyl gallate, lecithin, Vitamin Etocopherol, sesamin, sesamol, sesamolin, alpha-tocopherol, ascorbicacid, ascorbyl palmitate, fumaric acid, malic acid, sodiummetabisulfite, and EDTA. Specific antioxidant examples include, but arenot limited to: Ascorbic Acid: 0.001 to 5% w/w, Vitamin E Tocopherol:0.001 to 5% w/w, Tocopherol: 0.001 to 5% w/w, and combinations ofascorbic acid, vitamin E tocopherol, and tocopherol can be used for thisinvention.

Chelating agents can prevent or at least mitigate the degradation ofcannabinoids from metal ions in solution. Chelating agents include, butare not limited to, ethylenediaminetetraacetic acid (EDTA), phosphoricacid, polyphosphates, polysaccharides, citric acid, and any combinationthereof.

Preservatives can be used to prevent microbial spoilage. Thesepreservatives include: methylparabens, ethylparabens, propylparabens,butylparabens, sorbic acid, acetic acid, propionic acid, sulfites,nitrites, sodium sorbate, potassium sorbate, calcium sorbate, benzoicacid, sodium benzoate, potassium benzoate, calcium benzoate, sodiummetabisulfite, propylene glycol, benzaldehyde, butylated hydroxytoluene,butylated hydroxyanisole, formaldehyde donors, essential oils, citricacid, monoglyceride, phenol, mercury components and any combinationthereof. Specific examples include, but are not limited to, sodiumbenzoate and potassium sorbate.

Additionally, the pH can be lowered to prevent or retard microbialgrowth. Lowering the pH below 4.0 is sufficiently low enough to preventmicrobial growth for a minimum of 1 month.

Preservatives and/or stabilizers can be added during formulation.Depending on the nature of the preservative/stabilizer, it may becontained in either the oil phase, interfacial layer, or the aqueouscontinuous phase. Once dissolved, the preservatives and stabilizers arereleased into solution imparting their properties into the aqueoussystem. This allows beverage manufacturers the ability to instantlycreate shelf-stable cannabis-infused beverages. Beverages made this waycan resist microbial growth and chemical degradation for a minimum of 3months.

The composition can be used for treatment of a subject afflicted with orsuffering from nausea, muscular spasms, multiple sclerosis, uterinecramps, bowel cramps, a movement disorder, pain, migraine headache,vertigo, glaucoma, asthma, inflammation, insomnia, high blood pressure,cancer, anxiety, convulsions, depression or psychosis.

Accordingly, in another aspect, this disclosure provides a method oftreatment of a subject. The method comprises administering to a subjectafflicted with or suffering from nausea, muscular spasms, multiplesclerosis, uterine cramps, bowel cramps, a movement disorder, pain,migraine headache, vertigo, glaucoma, asthma, inflammation, insomnia,high blood pressure, cancer, anxiety, convulsions, depression orpsychosis, an effective amount of the composition as described above.

In some embodiments, the composition is administered intratumorally,intravenously, subcutaneously, intraosseously, orally, transdermally, insustained release, in controlled release, in delayed release, as asuppository, or sublingually. In some embodiments, the composition isadministered once, twice, three, or four times per day, or as needed.

The administration of the composition invention may be intermittent,bolus dose, or at a gradual or continuous, constant or controlled rateto a patient. In addition, the time of day and the number of times perday that the pharmaceutical formulation is administered may vary and arebest determined by a skilled practitioner such as a physician. Further,the effective dose can vary depending upon factors such as the mode ofdelivery, gender, age, and other conditions of the patient, as well asthe extent or progression of the disease. The compounds may be providedalone, in a mixture containing two or more of the compounds, or incombination with other medications or treatment modalities. Thecompounds may also be added to blood ex vivo and then be provided to thepatient.

In one aspect, this disclosure provides a kit comprising the compositionas described above. In some embodiments, the kit further comprising abeverage, wherein the composition and the beverage are in separatecontainers. In some embodiments, the kit may further includeinstructional materials.

“Instructional material,” as that term is used herein, includes apublication, a recording, a diagram, or any other medium of expressionthat can be used to communicate the usefulness of any composition and/orcompound of the invention in a kit. The instructional material of thekit may, for example, be affixed to a container that contains anycomposition of the invention or be shipped together with a containerwhich contains any composition. Alternatively, the instructionalmaterial may be shipped separately from the container with the intentionthat the recipient uses the instructional material and any compositioncooperatively. Delivery of the instructional material may be, forexample, by physical delivery of the publication or other medium ofexpression communicating the usefulness of the kit, or may alternativelybe achieved by electronic transmission, for example, by means of acomputer, such as by electronic mail, or download from a website.

Also within the scope of this disclosure is an edible product comprisingthe composition as described above. In some embodiments, the edibleproduct is selected from a lozenge, candy, chocolate, brownie, cookie,trail bar, cracker, dissolving strip, pastry, bread, or chewing gum.

TABLE 3 Experiment Results Summary Method CO2 Extraction CO2/HydrocarbonTrim Cannabinoids Trim Cannabinoids Potency Potency Efficiency PotencyPotency Efficiency (%) Results (%) (%) (%) Results (%) (%)  8% 52-57%56-59%  8% 75-83% 79-84%  9% 53-57% 57-60%  9% 77-86% 81-89% 10% 55-59%59-62% 10% 79-88% 83-92% 11% 56-62% 60-64% 11% 83-90% 87-93% 12% 62-64%63-66% 12% 86-92% 90-95%

D. Definitions

To aid in understanding the detailed description of the compositions andmethods according to the disclosure, a few express definitions areprovided to facilitate an unambiguous disclosure of the various aspectsof the disclosure. Unless otherwise defined, all technical andscientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this disclosurebelongs.

The term “cannabis” refers to plants of the genus cannabis, includingcannabis saliva, cannabis indica, and cannabis ruderalis.

The term “cannabis oil” refers to a mixture of compounds obtained fromthe extraction of cannabis plants. Such compounds include, but are notlimited to, cannabinoids, terpenes, terpenoids, and other compoundsfound in the cannabis plant. The exact composition of cannabis oil willdepend on the strain of cannabis that is used for extraction, theefficiency and process of the extraction itself, and any additives thatmight be incorporated to alter the palatability or improveadministration of the cannabis oil.

The term “cannabinoid” refers to a chemical compound that shows director indirect activity at a cannabinoid receptor. There are two maincannabinoid receptors, CNR1 (also known as CB1) and CNR2 (also known asCB2). Other receptors that research indicates have cannabinoid activityinclude the GPR55, GPR18, and TRPV1 receptors. The term“phytocannabinoid” refers to cannabinoids that occur in a plant speciesor are derived from cannabinoids occurring in a plant species. Examplesof cannabinoids include, but are not limited to, tetrahydrocannabinol(THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG),cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether(CBGM).

As used herein, CBD refers to cannabidiol.

As used herein, Δ⁹-THC refers to Δ⁹-tetrahydrocannabinol.

As used herein, Δ⁸-THC refers to Δ⁸-tetrahydrocannabinol.

The term “acidic cannabinoid” refers to a cannabinoid having one or morecarboxylic acid functional groups. Examples of acidic cannabinoidsinclude, but are not limited to, tetrahydrocannabinolic acid (THCA),cannabidiolic acid (CBDA), and cannabichromenic acid (CBC). Acidiccannabinoids are frequently the predominant cannabinoids found in raw(i.e., unprocessed) cannabis plant material.

The term “essential oil” refers to natural plant oil typically obtainedby distillation and having a chemical composition and organolepticproperties (e.g., fragrance) characteristic of the plant or othersources from which it is extracted.

As used herein, “anti-emetic” refers to compounds capable of reducingnausea, enhancing appetite and/or reducing vomiting in an individual.

By “water-soluble” we mean that 1 mg of material in 1 ml of water givesa clear solution and is water-miscible.

By “high affinity” we mean that the compounds exhibit a Ki in the rangeof about 0.03 nM to about 80 nM, and preferably from about 0.03 nM toabout 50 nM, for either the CB1 or CB2 receptors, or both.

As used herein, “effective amount” refers to the administration of anamount of a given compound that achieves the desired effect. Forexample, regarding the combination of CBD and Δ⁸-THC, an “effectiveamount” is an amount sufficient for or that is capable of reducingnausea or vomiting and/or enhancing appetite in a patient or individualin need of such treatment. The patient may be a human patient.

As used herein, “purified” does not require absolute purity but isinstead intended as a relative definition. For example, purification ofstarting material or natural material to at least one order ofmagnitude, preferably two or three orders of magnitude, is expresslycontemplated as falling within the definition of “purified.”

As used herein, the term “isolated” requires that the material beremoved from its original environment.

As used herein, the terms “subject” and “patient” are usedinterchangeably irrespective of whether the subject has or is currentlyundergoing any form of treatment. As used herein, the terms “subject”and “subjects” may refer to any vertebrate, including, but not limitedto, a mammal (e.g., cow, pig, camel, llama, horse, goat, rabbit, sheep,hamsters, guinea pig, cat, dog, rat, and mouse, a non-human primate (forexample, a monkey, such as a cynomolgus monkey, chimpanzee, etc) and ahuman). The subject may be a human or a non-human. In this context, a“normal,” “control,” or “reference” subject, patient or populationis/are one(s) that exhibit(s) no detectable disease or disorder,respectively.

“Sample,” “test sample,” and “patient sample” may be usedinterchangeably herein. The sample can be a sample of, serum, urineplasma, amniotic fluid, cerebrospinal fluid, cells (e.g.,antibody-producing cells) or tissue. Such a sample can be used directlyas obtained from a patient or can be pre-treated, such as by filtration,distillation, extraction, concentration, centrifugation, inactivation ofinterfering components, addition of reagents, and the like, to modifythe character of the sample in some manner as discussed herein orotherwise as is known in the art. The terms “sample” and “biologicalsample” as used herein generally refer to a biological material beingtested for and/or suspected of containing an analyte of interest such asantibodies. The sample may be any tissue sample from the subject. Thesample may comprise protein from the subject.

The term “treating” or “treatment” refers to administration of acompound or agent to a subject who has a disorder or is at risk ofdeveloping the disorder with the purpose to cure, alleviate, relieve,remedy, delay the onset of, prevent, or ameliorate the disorder, thesymptom of the disorder, the disease state secondary to the disorder, orthe predisposition toward the disorder.

The terms “prevent,” “preventing,” “prevention,” “prophylactictreatment” and the like refer to reducing the probability of developinga disorder or condition in a subject (e.g., plant), who does not have,but is at risk of or susceptible to developing a disorder or condition.

The terms “decrease,” “reduced,” “reduction,” “decrease,” or “inhibit”are all used herein generally to mean a decrease by a statisticallysignificant amount. However, for the avoidance of doubt, “reduced,”“reduction” or “decrease” or “inhibit” means a decrease by at least 10%as compared to a reference level, for example, a decrease by at leastabout 20%, or at least about 30%, or at least about 40%, or at leastabout 50%, or at least about 60%, or at least about 70%, or at leastabout 80%, or at least about 90% or up to and including a 100% decrease(e.g., absent level as compared to a reference sample), or any decreasebetween 10-100% as compared to a reference level.

It is noted here that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referenceunless the context clearly dictates otherwise.

The terms “including,” “comprising,” “containing,” or “having” andvariations thereof are meant to encompass the items listed thereafterand equivalents thereof as well as additional subject matter unlessotherwise noted.

The phrases “in one embodiment,” “in various embodiments,” “in someembodiments,” and the like are used repeatedly. Such phrases do notnecessarily refer to the same embodiment, but they may unless thecontext dictates otherwise.

The terms “and/or” or “/” means any one of the items, any combination ofthe items, or all of the items with which this term is associated.

The word “substantially” does not exclude “completely,” e.g., acomposition which is “substantially free” from Y may be completely freefrom Y. Where necessary, the word “substantially” may be omitted fromthe definition of the invention.

As used herein, the term “approximately” or “about,” as applied to oneor more values of interest, refers to a value that is similar to astated reference value. In some embodiments, the term “approximately” or“about” refers to a range of values that fall within 25%, 20%, 19%, 18%,17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%,1%, or less in either direction (greater than or less than) of thestated reference value unless otherwise stated or otherwise evident fromthe context (except where such number would exceed 100% of a possiblevalue). Unless indicated otherwise herein, the term “about” is intendedto include values, e.g., weight percents, proximate to the recited rangethat are equivalent in terms of the functionality of the individualingredient, the composition, or the embodiment.

As disclosed herein, a number of ranges of values are provided. It isunderstood that each intervening value, to the tenth of the unit of thelower limit, unless the context clearly dictates otherwise, between theupper and lower limits of that range is also specifically disclosed.Each smaller range between any stated value or intervening value in astated range and any other stated or intervening value in that statedrange is encompassed within the invention. The upper and lower limits ofthese smaller ranges may independently be included or excluded in therange, and each range where either, neither, or both limits are includedin the smaller ranges is also encompassed within the invention, subjectto any specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

As used herein, the term “each,” when used in reference to a collectionof items, is intended to identify an individual item in the collectionbut does not necessarily refer to every item in the collection.Exceptions can occur if explicit disclosure or context clearly dictatesotherwise.

The use of any and all examples or exemplary language (e.g., “such as”)provided herein, is intended merely to better illuminate the inventionand does not pose a limitation on the scope of the invention unlessotherwise claimed. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

All methods described herein are performed in any suitable order unlessotherwise indicated herein or otherwise clearly contradicted by context.In regard to any of the methods provided, the steps of the method mayoccur simultaneously or sequentially. When the steps of the method occursequentially, the steps may occur in any order, unless noted otherwise.In cases in which a method comprises a combination of steps, each andevery combination or sub-combination of the steps is encompassed withinthe scope of the disclosure, unless otherwise noted herein.

Each publication, patent application, patent, and other reference citedherein is incorporated by reference in its entirety to the extent thatit is not inconsistent with the present disclosure. Publicationsdisclosed herein are provided solely for their disclosure prior to thefiling date of the present invention. Nothing herein is to be construedas an admission that the present invention is not entitled to antedatesuch publication by virtue of prior invention. Further, the dates ofpublication provided may be different from the actual publication dates,which may need to be independently confirmed.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims.

E. EXAMPLES Example 1

Stepwise Time-dependent Extraction of Terpenes and Cannabinoids

As a novel application for the disclosed CO₂/Hydrocarbon extractionsystem, fresh frozen material (about −5 to −10° C.) can be used to feedthe reactor. The CO₂/Hydrocarbon system also further provides a coolerenvironment for the reactor, which will reduce the temperature insidethe reactor to −30 to −50° C. (depends on the mixture ratio and gasaccumulator pressure). In a timeframe of 5 to 30 minutes, high purityterpenes profiles can be extracted. After 30 minutes, high potency oilwith lower terpene profiles can be extracted. Since fresh frozen isalready cold with changing gas solvent accumulator (range from 200 psito 550 psi), it will get lower temperatures in the reactor compared tothe fresh one. Although the 400 to 450 psi is the optimum pressurerange. Having a pressure of 400 to 450 psi in the gas accumulator willresult in the temperature range of −40 to −50 C in the reactor. In oneexperiment, 72 grams of terpenes can be extracted in the first 30minutes, and 355 grams of oil can be extracted in 20 hours, from about7.0 kg fresh frozen at 10% and over 50 wt % water.

The disclosed methods and systems are advantageous compared to the freshfrozen hydrocarbon (70% Butane/30% Propane) extraction system, because asignificantly lower amount of crystal THCa will be produced along withterpenes.

What is claimed is:
 1. A method for cannabis extraction, comprising: (i)contacting cannabis plant material with a supercritical fluid solventsystem comprising carbon dioxide (CO₂) and a hydrocarbon co-solvent;(ii) obtaining a first fraction of the supercritical fluid solventsystem containing a first cannabis extract during a first period oftime; (iii) obtaining a second fraction of the supercritical fluidsolvent system containing a second cannabis extract during a secondperiod of time; and (iv) removing the CO₂ and the hydrocarbon co-solventfrom the first fraction of the supercritical fluid solvent system andthe second fraction of the supercritical fluid solvent system, therebyobtaining the first cannabis extract and the second cannabis extract. 2.The method of claim 1, wherein the first cannabis extract comprisesterpene and the second cannabis extract comprises cannabinoids.
 3. Themethod of claim 1, wherein the cannabis plant material comprises freshfrozen.
 4. The method of claim 1, wherein the first period of time isbetween about 2 minutes and about 30 minutes and the second period oftime is between about 30 minutes and about 24 hours.
 5. The method ofclaim 1, wherein the hydrocarbon co-solvent is selected from the groupconsisting of propane, propene, propadiene, and a combination thereof.6. The method of claim 1, wherein a molar ratio of carbon dioxide to thehydrocarbon co-solvent is (i) between about 0.75 to about 0.25 and about0.98 to about 0.02 or (ii) between about 0.95 to about 0.05.
 7. Themethod of claim 1, wherein the step of contacting is performed at apressure between about 650 psi and about 800 psi.
 8. The method of claim1, wherein the step of contacting is performed at a temperature betweenabout 32° F. and about 38° F.
 9. The method of claim 1, comprisingrepeating steps (a) and (b) at least once.
 10. The method of claim 1,wherein the cannabis extract comprises terpene oil.
 11. The method ofclaim 1, wherein the extraction efficiency of terpene is at least 50%higher than a predetermined reference value.
 12. The method of claim 1,wherein the cannabis extract comprises one or more cannabinoids selectedfrom the group consisting of: tetrahydrocannabinol (THC), cannabidiol(CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC),cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV),cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin(CBGV), cannabigerol monomethyl ether (CBGM), and a combination thereof.13. The method of claim 1, wherein the cannabis plant material isprocessed from Cannabis sativa or Cannabis indica.
 14. The method ofclaim 14, further comprising grinding Cannabis sativa or Cannabis indicainto ground cannabis plant material.
 15. The method of claim 1, whereinthe wax formation is reduced by at least 10% compared to a predeterminedreference value.
 16. The method of claim 1, further comprising purifyingthe cannabis extract by employing at least one of chromatography,adsorption, crystallization, distillation, liquid-liquid extraction,filtration, fractional distillation, precipitation, recrystallization,and sublimation.
 17. A system for cannabis extraction, comprising: atleast one extractor configured to receive plant material and asupercritical fluid solvent system comprising carbon dioxide (CO₂) and ahydrocarbon co-solvent; an accumulator connected to the extractor andconfigured to feed the supercritical fluid solvent system to theextractor; and at least one container connected to the extractor andconfigured to receive the extract generated from the plant material. 18.The system of claim 18, wherein the plant material is cannabis plantmaterial or coffee or tea leaves.
 19. The system of claim 18, furthercomprising a first reservoir for CO₂ and a second reservoir for thehydrocarbon co-solvent, wherein the first reservoir and the secondreservoir are connected to the accumulator and configured to feed CO₂and the hydrocarbon co-solvent to the accumulator in which CO₂ and thehydrocarbon co-solvent are blended at a predetermined molar ratio.